Background
Recent evidence indicates that Staphylococcus aureus, one of the most important human pathogens, secretes vesicles into the extracellular milieu.
Objective
To evaluate whether inhalation ...of S. aureus‐derived extracellular vesicles (EV) is causally related to the pathogenesis of inflammatory pulmonary diseases.
Methods
Staphylococcus aureus EV were prepared by sequential ultrafiltration and ultracentrifugation. The innate immune response was evaluated in vitro after the application of EV to airway epithelial cells and alveolar macrophages. In vivo innate and adaptive immune responses were evaluated after airway exposure to EV. Adjuvant effects of EV on the development of hypersensitivity to inhaled allergens were also evaluated after airway sensitization with S. aureus EV and ovalbumin (OVA).
Results
Staphylococcus aureus and S. aureus EV were detected in house dust. Alveolar macrophages produced both tumor necrosis α (TNF‐α) and interleukin 6 (IL‐6) after in vitro stimulation with S. aureus EV, whereas airway epithelial cells produced only IL‐6. Repeated airway exposure to S. aureus EV induced both Th1 and Th17 cell responses and neutrophilic pulmonary inflammation, mainly via a Toll‐like receptor 2 (TLR2)‐dependent mechanism. In terms of adjuvant effects, airway sensitization with S. aureus EV and OVA resulted in neutrophilic pulmonary inflammation after OVA challenge alone. This phenotype was partly reversed by the absence of interferon γ (IFN‐γ) or IL‐17.
Conclusion
Staphylococcus aureus EV can induce Th1 and Th17 neutrophilic pulmonary inflammation, mainly in a TLR2‐dependent manner. Additionally, S. aureus EV enhance the development of airway hypersensitivity to inhaled allergens.
The effects of Al on microstructure, stacking fault energy, tensile properties and fractured surface in Fe–18Mn–0.6C–(0–2)Al twinning-induced plasticity (TWIP) steels were systemically investigated. ...The Al addition suppressed the cementite precipitation during cooling after hot-rolling. The stacking-fault energy was linearly raised with a constant slope of 7.8mJm−2 per 1 wt.% Al. The Al addition increased the yield stress, reduction in area, uniform (eu), and post-uniform (epu) elongations, while it decreased the amount and rate of strain hardening and dynamic strain aging (DSA). In particular, although the epu of the TWIP steel without Al was almost zero, it was improved up to ∼7% by addition of 2 wt.% Al, which was comparable with those of dual phase and TRIP steels with a similar tensile strength of 780MPa. In order to elucidate the reasons for the poor epu in C-bearing TWIP steel and for the prolonged epu by Al addition, the apparent absolute strain-rate sensitivity m=dσ/dlnε˙ of two TWIP steels with different Al concentrations of 0 and 2 wt.% was investigated at room temperature. Both TWIP steels had negative strain-rate sensitivity at a large strain (ε=0.4) of just before necking. However, the Al addition increased the strain-rate sensitivity, resulting in improved epu because of reduced DSA by decreases in both activity and diffusivity of C in austenite.
Metastasis is the predominant cause of death in breast cancer patients. Several lines of evidence have shown that microRNAs (miRs) can have an important role in cancer metastasis. Using isogenic ...pairs of low and high metastatic lines derived from a human breast cancer line, we have identified miR-149 to be a suppressor of breast cancer cell invasion and metastasis. We also identified GIT1 (G-protein-coupled receptor kinase-interacting protein 1) as a direct target of miR-149. Knockdown of GIT1 reduced migration/invasion and metastasis of highly invasive cells. Re-expression of GIT1 significantly rescued miR-149-mediated inhibition of cell migration/invasion and metastasis. Expression of miR-149 impaired fibronectin-induced focal adhesion formation and reduced phosphorylation of focal adhesion kinase and paxillin, which could be restored by re-expression of GIT1. Inhibition of GIT1 led to enhanced protein degradation of paxillin and α5β1 integrin via proteasome and lysosome pathways, respectively. Moreover, we found that GIT1 depletion in metastatic breast cancer cells greatly reduced α5β1-integrin-mediated cell adhesion to fibronectin and collagen. Low level of miR-149 and high level of GIT1 was significantly associated with advanced stages of breast cancer, as well as with lymph node metastasis. We conclude that miR-149 suppresses breast cancer cell migration/invasion and metastasis by targeting GIT1, suggesting potential applications of the miR-149-GIT1 pathway in clinical diagnosis and therapeutics.
A record power conversion efficiency (PCE) of over 19% is realized in planar‐mixed heterojunction (PMHJ) organic solar cells (OSCs) by adopting the asymmetric selenium substitution strategy in making ...a pseudosymmetric electron acceptor, BS3TSe‐4F. The combined molecular asymmetry with more polarizable selenium substitution increases the dielectric constant of the D18/BS3TSe‐4F blend, helping lower the exciton binding energy. On the other hand, dimer packing in BS3TSe‐4F is facilitated to enable free charge generation, helping more efficient exciton dissociation and lowering the radiative recombination loss (ΔE2) of OSCs. As a result, PMHJ OSCs based on D18/BS3TSe‐4F achieve a PCE of 18.48%. By incorporating another mid‐bandgap acceptor Y6‐O into D18/BS3TSe‐4F to form a ternary PMHJ, a higher open‐circuit voltage (VOC) can be achieved to realize an impressive PCE of 19.03%. The findings of using pseudosymmetric electron acceptors in enhancing device efficiency provides an effective way to develop highly efficient acceptor materials for OSCs.
A pseudosymmetric electron acceptor, BS3TSe‐4F, designed from asymmetric selenium substitution strategy promotes free charge generation to enhance exciton dissociation and suppress energy loss in sequentially processed organic solar cells, leading to a record power conversion efficiency of over 19%.
Aims
Exopolysaccharide fraction from Pediococcus pentosaceus KFT18 (PE‐EPS), a lactic acid bacteria isolated from Kimchi (a Korean fermented vegetable product), was preliminary characterized and its ...immunostimulating effects were analysed.
Methods and Results
In this study, we used interferon‐γ (IFN‐γ)‐primed RAW 264·7 macrophages and CD3/CD28‐stimulated splenocytes to determine the immunotimulatory activities of PE‐EPS. Upon exposure to PE‐EPS, IFN‐γ‐primed RAW 264·7 macrophages showed significant increases in the expressions of inducible nitric oxide synthase (iNOS), tumour necrosis factor‐α (TNF‐α), interleukin (IL)‐6 and IL‐1β. Molecular data using reporter gene assay and electrophoretic mobility shift assay (EMSA) revealed that PE‐EPS upregulated transcriptional activity, DNA binding and the nuclear translocation of nuclear factor‐κB (NF‐κB). Furthermore, PE‐EPS enhanced anti‐CD3/CD28‐specific proliferation and the productions of IL‐2 and IFN‐γ in primary splenocytes. In cyclophosphamide‐induced immunosuppressed mice, pretreatment with PE‐EPS (5, 15 or 45 mg kg−1 day−1, p.o.) increased thymus and spleen indices, and improved lymphocyte and neutrophil counts.
Conclusion
PE‐EPS stimulated the IFN‐γ‐primed macrophages and primary splenocytes to induce immune responses and improved the cyclophosphamide‐induced immunosuppression in mice.
Significance and Impact of the Study
The results in this study improved our understanding of immunostimulating activity of PE‐EPS and supported its potential treatment option as a natural immunostimulant.
Over the past few decades, tetrafluoroethane (TFE, R134a Freon)-based gases have been widely used in the operation of phenolic resistive plate chambers (RPCs) in many high-energy experiments. ...However, TFE has a high global warming potential (GWP); therefore, a search for new eco-friendly gases to replace traditional TFE-based ones is now unavoidable. In this research, we present cosmic-ray test results of a prototype RPC for the SHiP (search for hidden particles) experiment using 1.6- and 1.4-mm-thick RPC electrodes containing mixtures of various gases, including 1,3,3,3-tetrafluoropropene (HFO1234ze), CO
2
,
i
C
4
H
10
and SF
6
. We compare the performance data gathered with these new gas mixtures with those gathered with a traditional TFE-based gas used for RPCs in compact muon solenoid (CMS) and a toroidal LHC apparatus (ATLAS) experiments. The addition of CO
2
to the HFO1234ze-based gas was found to be fairly effective in reducing the working-point high voltage (HV
WP
) for RPC operation. The results of our experiments lead us to the conclusion that adding 40% CO
2
or less, when combined with HFO1234ze-based gas, is conducive to reliable detector performance for SHiP single-gap phenolic RPCs.
The antiferroelectricity in HfZrO 2 (HZO) annealed at 600 °C with an abrupt turn ON of FET characteristics with SSmin = 23 mV/dec and SSavg = 50 mV/dec over 4 decades of IDS is demonstrated. The near ...non-hysteresis is achieved with an antiferroelectric-like HZO due to a small remanent polarization and a coercive field. A feasible concept of coupling the antiferroelectric and ferroelectric type HZO are used for low-power electronics and the memory applications, respectively.
The metastable high- and medium entropy alloys (HEAs or MEAs) have drawn many attentions regarding deformation mechanisms and mechanical properties. Most of their studies have conducted under ...quasi–static or uniaxial tensile/compressive loading conditions. For cryogenic applications, however, the fracture or impact toughness should be carefully evaluated because it is one of the most important indices for the low–temperature performance. In this study, quasi–static and dynamic tensile properties of a metastable VCrFeCoNi HEA were investigated at room and cryogenic temperatures, and they were systematically correlated with the Charpy impact toughness. Under the quasi–static tensile loading, the Twinning Induced Plasticity (TWIP) mechanism occurred at room temperature, while the Transformation Induced Plasticity (TRIP) from FCC to BCC phases via an intermediate HCP phase occurred at cryogenic temperature. Under the dynamic loading, more deformation twins were formed at room temperature, and the amount of martensite reduced at cryogenic temperature. These variations of twinning and martensitic transformation were elucidated by the raised flow stress and by the adiabatic heating effect, respectively. They were confirmed by combining with ab–initio calculations, leading to the strong dependency of the energetic stability of BCC and HCP phases relative to the FCC phase. As a result, a plenty of deformation twins under the dynamic loading resulted in the high impact toughness of 112.6 J at room temperature. The martensitic transformation and consequently refined network structure played key roles in sustaining the remarkable toughness and in preventing the DBT phenomenon as the test temperature decreased.
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•The differences in Gibbs energy between phases work as a significant parameter for explaining the TWIP to TRIP transition.•When the loading changes from the quasi–static to dynamic one, abundant twin formation and reduction in TRIP amount occur.•Charpy impact toughness maintained almost constant as the test temperature decreased.•This dynamic grain–refinement effect could play a key role in preventing the ductile-to-brittle transition phenomenon.
Summary
Bone mineral density (BMD) is significantly decreased after gastrectomy in patients with gastric cancer. Calcium malabsorption, secondary hyperparathyroidism, and dominant bone resorption ...appear to contribute to bone loss in these patients. Patients should undergo early surveillance and nutritional or pharmacologic intensive interventions for bone health.
Purpose
Survivorship care, including bone health, has become an important issue in gastric cancer. We performed a meta-analysis of the available observational studies to determine whether and how osteoporosis risk is increased after gastrectomy in patients with gastric cancer.
Methods
A total of 1204 patients (802 men) from 19 cohort studies were included. We evaluated the prevalence of osteoporosis in postgastrectomy patients, comparing the incidence according to the type of gastrectomy and sex. Additionally, we evaluated changes in bone mineral density (BMD) and bone metabolism-related markers pre- to postoperatively and between patients who underwent gastrectomy and matched controls. Proportion meta-analysis was performed and pooled odds ratios (ORs) were calculated.
Results
The pooled incidence estimate was 36% 95% confidence interval (CI), 32–40. The incidence of osteoporosis was significantly higher in women than in men (OR = 1.90,
p
< 0.001) but was similar between partial and total gastrectomy groups (OR = 0.983,
p
= 0.939). BMD was significantly decreased, and calcium, phosphorous, and parathyroid hormone levels were significantly increased in patients after gastrectomy compared to those before gastrectomy. BMD and calcium and 25OH-vitamin D levels were significantly decreased, and parathyroid hormone and 1,25OH-vitamin D levels were significantly increased in the gastrectomy group compared to that in the control group.
Conclusion
We found that BMD is significantly decreased after gastrectomy in patients with gastric cancer. Vitamin D deficiency and secondary hyperparathyroidism are suggested to be common mechanism underlying BMD impairment. After resection, patients should undergo long-term nutritional and bone health surveillance, in addition to their oncological follow-up.